PMID: 16520660Mar 8, 2006Paper

MLH1-deficient tumor cells are resistant to lipoplatin, but retain sensitivity to lipoxal

Anti-cancer Drugs
André FedierDaniel Fink

Abstract

Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is dependent on the functional integrity of DNA mismatch repair (MMR), a post-replicative DNA repair machinery implicated in cell cycle control and apoptosis. Clonogenic data revealed a significant (P<0.05) 2-fold resistance to lipoplatin of HCT116 human colorectal adenocarcinoma cells lacking MLH1, one of five proteins crucial to MMR function, as compared to MLH1-expressing HCT116 cells. In addition, MLH1-deficient cells were at least 3-fold less susceptible to apoptosis (DNA fragmentation) than MLH1-proficient cells. However, proteolytic processing of caspase-3, caspase-7 and poly(ADP-ribose)polymerase-1 following lipoplatin treatment was comparable in MLH1-deficient cells and -proficient cells. Furthermore, MLH1-deficient cells retained the ability to attenuate cell cycle progression past the G2/M checkpoint following lipoplatin treatment. In conclusion, our results indicate that the lipoplatin-sensitive phenotype of M...Continue Reading

References

Jun 1, 1995·Current Opinion in Genetics & Development·R Fishel, R D Kolodner
Nov 1, 1994·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·P Karran, M Bignami
Oct 1, 1995·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·M J McKeage
Jan 1, 1996·Annual Review of Biochemistry·P Modrich, R Lahue
Feb 5, 1999·The Biochemical Journal·G Marra, P Schär
Mar 11, 1999·Current Opinion in Genetics & Development·R D Kolodner, G T Marsischky
Jan 7, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H J MackayR Brown
Mar 22, 2001·Molecular Pharmacology·V M GonzalezJ M Perez
Jul 31, 2001·International Journal of Cancer. Journal International Du Cancer·A FedierD Fink
Jan 12, 2002·Nature Medicine·Koert N J BurgerBen de Kruijff
Jun 18, 2002·Trends in Molecular Medicine·Ida S Mathiasen, Marja Jäättelä
Aug 15, 2002·Journal of Inorganic Biochemistry·Deborah B ZambleStephen J Lippard
Mar 5, 2003·Biochemistry·Yongwon Jung, Stephen J Lippard
Apr 7, 2004·Trends in Cell Biology·Mary C Abraham, Shai Shaham
Jul 29, 2004·DNA Repair·Lovorka StojicJosef Jiricny

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Citations

Sep 10, 2011·Journal of Drug Delivery·G P Stathopoulos, T Boulikas
Nov 1, 2009·Future Medicinal Chemistry·Susanne Bryde, Anton I P M de Kroon
Feb 16, 2012·Journal of Liposome Research·Gina SongWilliam C Zamboni
Jul 17, 2009·Expert Opinion on Investigational Drugs·Teni Boulikas
Oct 12, 2013·Advanced Drug Delivery Reviews·Hardeep S OberoiTatiana K Bronich
Jun 17, 2015·Gynecologic Oncology·Stéphanie DecollognePierre J Dilda
Mar 30, 2021·Journal of Experimental Pharmacology·Paul B TchounwouSanjay Kumar
May 1, 2021·Cancers·Beate Köberle, Sarah Schoch

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